Cases reported "Multiple Myeloma"

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1/29. T-cell-epitope mapping of the idiotypic monoclonal IgG heavy and light chains in multiple myeloma.

    The idiotypic structures of the myeloma protein might be regarded as tumor-specific antigens. The present study was designed to map T-cell epitopes of the idiotypic myeloma protein to prove the existence of naturally occurring major-histocompatibility-complex-dependent idiotype (peptide)-specific T cells in multiple myeloma. The fine specificity of idiotype-reactive, interferon-gamma-producing blood T cells of a patient with multiple myeloma stage I was characterized by identification of idiotype (heavy and light chains)-derived MHC-restricted T-cell epitopes. T cells specifically reacting with peptides corresponding to each of the 3 complementarity-determining regions (CDRs) of the heavy-chain variable part (V(H)) of the autologous idiotype were found. In contrast, none of the peptides corresponding to the 3 CDRs of the light chain (V(L)) induced a specific T-cell response. The idiotype amino-acid sequence corresponding to the junction of the V(H), diversity (D), and joining (J) gene segments of the VH appeared to be an important target for T cells, since the sequence expressed MHC-class-I- as well as MHC-class-II-restricted epitopes. The study provides further support for the existence of MHC-restricted idiotype-specific T cells, which may target immunogenic CDR peptides in multiple myeloma. Such T cells could be an important part of the specific anti-tumor immune responses induced in idiotype vaccination protocols.
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2/29. Late appearance of an IgA (kappa) monoclonal protein in a patient with IgG (kappa) multiple myeloma: sharing of idiotypic specificities between the two serum proteins.

    A patient with an IgG(chi) monoclonal serum protein developed in the course of the disease a second monoclonal spike of the same light chain type and of the IgA class. The latter monoclonal protein progressively increased and eventually exceeded the first IgG(chi) protein. Antigenic analysis of the two myeloma proteins demonstrated that they shared idiotypic determinants. Immunofluorescence studies, carried out with anti gamma and anti alpha reagents tagged with different fluorochromes revealed that the two isotypes were produced by different plasma cells. The data are discussed in the prospect of a possible transitional mechanism from IgG to IgA synthesis within a single B cell clone.
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3/29. Generation of anti-idiotype immune responses following vaccination with idiotype-protein pulsed dendritic cells in myeloma.

    Myeloma cells produce immunoglobulin which is unique to the malignant clone and presents antigenic determinants, or idiotypes, which may function as a tumour-specific antigen. The availability of significant quantities of idiotype protein in the serum makes immunotherapeutic strategies utilizing this protein to generate an anti-idiotype immune response an attractive prospect. We treated two patients with advanced refractory myeloma with a series of four vaccinations using autologous idiotype-protein pulsed dendritic cells combined with adjuvant GM-CSF. The vaccinations were well tolerated with a mild fever post-vaccination in one patient. An idiotype-specific T-cell proliferative response developed in both patients. This T-cell response was associated with the production of gamma-interferon, indicating a TH-1-like response. Furthermore, one patient developed anti-idiotype IgM antibodies. However, no idiotype-specific cytotoxic T-cell response could be demonstrated. Further investigation is warranted to define the optimal conditions for dendritic cell culture and priming to maximize the anti-tumour immune response.
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4/29. Crystal nephropathy: a variant form of myeloma kidney--a case report and review of the literature.

    Cast nephropathy is the most common form of myeloma kidney, and also one of the major determinants of a patient's prognosis. We experienced a case of multiple myeloma with acute renal failure that was associated with massive crystal deposition in kidney and bone marrow. Large crystal formation in myeloma kidney is a rare pathological finding in renal biopsies. In the literature, most of the cases with multiple myeloma with extracellular crystal deposition often have a rapidly progressive course with a poor prognosis. Ball et al. [1993] suggested that this type of extracellular crystal deposition be designated as "crystalglobulinemia syndrome". The characteristics of the clinical and histopathological features, rapid progression and poor outcome, and crystal formation in the tubules found in the present case and in those previously reported, support the proposal of a new concept of "crystal nephropathy".
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5/29. Cardiac amyloidosis presenting with elevations of cardiac troponin i and angina pectoris.

    We present the case of a 43-year-old male who was initially evaluated for angina pectoris and dyspnea. His CK, CK-MB, and cTnI were all elevated following a blood transfusion and he underwent coronary arteriography, which demonstrated no luminal obstructions. After several months, he was transferred to Mayo Clinic where diagnoses of fulminant cardiac amyloidosis and systemic multiple myeloma were established. The cTnI remained elevated despite normalization of the CK and CK-MB. Despite aggressive treatment, the patient died. Postmortem analysis demonstrated amyloid cardiac deposition including involvement of the coronary microvasculature. Electron microscopy revealed myocyte compression injury from amyloid infiltration. We believe this is the first report of elevated troponin i in a patient with cardiac amyloidosis. The electron microscopy in our case confirms cardiac damage as the mechanism for cTnI elevation. This observation strengthens our knowledge about the specificity of cTnI for the detection of cardiac injury.
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6/29. Idiotype in myeloma terminating in erythroleukemia.

    A patient with multiple myeloma, IgG kappa type, developed erythroleukemia with cytogenetic abnormalities three years after diagnosis. The latter disease progressed terminally to acute granulocytic leukemia. Anti-idiotype antibody reagents were prepared by injecting rabbits with the purified monoclonal IgG kappa obtained from the patient's serum and subsequent absorption of the antisera with normal IgG coupled to sepharose 4B. These reagents reacted specifically with autologous myeloma cells but failed to react with all tested allogeneic cells: these included myeloma cells, reactive lymphocytes and plasma cells, and established lymphoid cell lines. Common idiotypic determinants were found in lymphoid and plasmacytic cells of the patient's marrow, spleen, lymph node, and gastrointestinal tract at autopsy that were not present in the leukemic population. The findings indicate that myeloma and granulocytic leukemia cells have separate clonal origins.
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7/29. multiple myeloma in remission complicated by bone marrow granulomas.

    BACKGROUND: Granulomas are encountered in 1-2% of biopsies performed in various hematological and non-hematological diseases. Almost 50% of bone marrow granulomas are associated with infections and 25% with hematologic disorders, especially lymphoma and multiple myeloma. toxoplasmosis is reported to induce granulomas in bone marrow inmunosuppressed patients. On the other side, long-term unexplained remissions after conventional treatment in multiple myeloma were mentioned in up to 10% of cases. CASE REPORT: A 56-years-old female patient was diagnosed with IgG(kappa) multiple myeloma in 1992. After 5 years, being still in complete remission, frequent bone marrow epithelioid non-caseating granulomas were noticed in biopsy, without clinical symptomatology or modifications of routine paraclinical examinations. The history revealed no treatments with antiarrhythmic, antihypertensive, anticonvulsivants or nonsteroid antiinflammatory drugs. The serologic tests for other infections or systemic diseases known to induce granulomas were negative, except those for toxoplasma gondii IgG. The treatment with azithromycine and pyrimethamine induced the disappearance of granulomas, simultaneously with an important decrease of anti-toxoplasma IgG antibodies titer. CONCLUSIONS: The bone marrow granulomas provide a valuable histologic clue to opportunistic infections and the bone marrow biopsy is useful for their diagnosis. In the specific case of toxoplasmosis, a recently proposed treatment with azithromycin induced the resolution of the granulomas. Due to the usual lack of specificity of the most bone marrow granulomas, a broad and long-term clinical, histopatological and serological follow-up to establish the etiology should be performed.
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keywords = specificity
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8/29. Idiotypical identity of IgG myeloma protein with monoclonal IgM, bence jones protein, and Fv derived from one patient.

    serum from a patient (KK) with IgG2-lambda myeloma was shown to contain multiple paraproteins corresponding to an IgM-lambda monoclonal protein (MMP), a lambda-type bence jones protein (BJP), and a 30 kDa component in addition to the IgG2 myeloma protein (GMP). These proteins possessed common idiotypic determinants, as judged by their monoclonal reactivity with rabbit anti-GMP idiotype antibody (aId) in the immunofixation electrophoresis. Analysis with aId absorbed with either H or L chain of GMP revealed that the 30 kDa component shared both VH and VL with GMP and MMP, while BJP carried only the VL idiotype. The 30 kDa component, however, failed to react with antibody to either the mu, gamma, alpha, kappa, or lambda isotype, indicating that it had an Fv-like molecular composition. These results suggest that myeloma cells of KK had diverged from the same precursor B cell clone to produce MPs of different isotypes and altered molecular constructions.
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keywords = determinant
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9/29. Simultaneous production of IgG lambda and IgA lambda in a clone of myeloma cells.

    We describe a patient (KY) with multiple myeloma and double paraproteinemia. The patient's serum contained IgG lambda and IgA lambda myeloma proteins. An anti-idiotypic antiserum to purified KY IgA was prepared in rabbits, and it was found that KY IgA and KY IgG shared common antigenic determinants, which appeared to be located in variable regions of both the heavy and light chains. Double staining experiments using an anti-alpha chain antibody conjugated with fluorescein isothiocyanate and anti-gamma chain antibody conjugated with rhodamine showed that virtually all plasma cells were stained for both antibodies simultaneously.
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ranking = 12.036009780339
keywords = determinant
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10/29. A myeloma paraprotein with specificity for platelet glycoprotein IIIa in a patient with a fatal bleeding disorder.

    Impaired platelet aggregation, normal shape change, and agglutination and normal ATP secretion and thromboxane synthesis in response to high concentrations of thrombin or arachidonic acid were found in a patient with multiple myeloma and hemorrhagic tendency. The purified IgG1 kappa or its F(ab1)2 fragments induced similar changes when added in vitro to platelet-rich plasma from normal subjects. In addition, the paraprotein inhibited adhesion to glass microbeads, fibrin clot retraction, and binding of radiolabeled fibrinogen or von willebrand factor to platelets exposed to thrombin or arachidonic acid without affecting intraplatelet levels of cAMP. The radiolabeled para-protein bound to an average of 35,000 sites on normal platelets but it bound to less than 2,000 sites on the platelets from a patient with Glanzmann's thrombasthenia. immunoprecipitation studies showed that the platelet antigen identified by the paraprotein was the glycoprotein IIIa. Furthermore, binding of radiolabeled prostaglandin E1 (PGE1) to resting platelets as well as binding of von willebrand factor to platelets stimulated with ristocetin were entirely normal in the presence of patient's inhibitor. These studies indicate that bleeding occurring in dysproteinemia may be the result of a specific interaction of monoclonal paraproteins with platelets. In addition, our data support the concept that the interaction of fibrinogen and/or von willebrand factor with the platelet glycoprotein IIb-IIIa complex is essential for effective hemostasis.
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